Acute renal and hepatic failure associated with allopurinol treatment.

Hyperuricemia is present in about 5% of the population, and allopurinol is frequently used to treat it. The use of this drug can be associated with a number of side effects, indicating allergic reactions, such as skin rash, reversible after its withdrawal. In some cases more severe hypersensitivity reactions may be seen, such as erythema multiforme exudativum, or Steven-Johnson Syndrome (SJS). Reversible clinical hepatotoxicity, as well as acute renal failure, may also develop after allopurinol therapy. We describe here the case of a 74-year-old woman with chronic renal failure who was admitted to hospital after 1 week of sore throat and fever, presenting mucous membrane lesions, widespread blistering of the skin, evolving to flaccid vesicles and bullae, and extensive epidermal detachment associated with acute renal failure and cholestatic jaundice. A diagnosis of allopurinol-induced toxic epidermal necrolysis (TEN) was established. Allopurinol was discontinued, and intensive care management was required: the patient was successfully treated by using intravenous immunoglobulin (IVIg), standard hemodialysis, and albumin dialysis (Molecular Adsorbents Recirculating System - MARS, Teraklin AG, Rostock, Germany). Allopurinol-induced TEN is extremely rare, however, the survival rate is extremely low. Clinicians should be aware of this potentially severe adverse effect. This report emphasizes the importance of an aggressive pharmacological and dialysis treatment in the case of TEN.

Principal component analysis of some oxidative stress parameters and their relationships in hemodialytic and transplanted patients.

BACKGROUND: Oxidative stress profoundly influences the biochemistry of proteins and many other molecules in tissues of uremic patients. In three different groups of uremic patients, the concentrations of the free and bound pentosidine and low-molecular-weight-advanced glycoxydation end products (LMW-AGEs), carbonyls (LMW-C), advanced oxidation protein products (AOPP) and the total antioxidant power of serum were studied in order to determine the relationships between these factors in hemodialytic and transplanted patients. PATIENTS AND METHODS: The above-mentioned parameters were determined in 10 subjects who were currently in hemodialysis (HD) treatment, 10 kidney transplanted patients with chronic renal failure (Tx-CRF), 10 kidney transplanted patients with normal renal function (Tx-N) and 10 healthy subjects (Ctr). The data matrix (40x7) was analyzed using the principal component analysis (PCA). RESULTS: AGEs, carbonyls and AOPP were strongly correlated, while the total antioxidative serum capacity was not related to the other oxidative stress parameters. All the oxidative stress-related parameter values (AGEs, AOPP and LMW-C) in the Tx patients were similar to those of the control group, but were higher in the patients with chronic renal failure. CONCLUSIONS: The correlation between early and advanced oxidative stress markers indicates that reactive oxygen species are involved in a common step in the mechanism of protein modification in all the patient examined. The relationships between carbonyls and AGEs (free, bound pentosidine and LMW-AGEs) support the hypothesis of "carbonyl stress". The common mechanism of the formation of oxidation products in healthy and diseased subject suggests their role of detoxification within kidney function. The total antioxidant power of the serum is not related to the other parameters, which indicates a possible role of molecule interfering.

Normalization of oxidative stress parameters after kidney transplant is secondary to full recovery of renal function.

BACKGROUND: It is well-known that hemodialysis patients experience increased oxidative stress, which is believed to cause numerous uremia-related complications. Retention of water-soluble toxins as well as protein-bound toxins is due to renal failure. Kidney transplantation restores, at least partially, the fundamental processes of glomerular filtration which eliminates toxic solutes. The aim of this study was to determine the levels of several different glycoxydative stress-related parameters after kidney transplantation. PATIENTS AND METHODS: A cross-sectional study was carried out on 30 subjects: 10 kidney-transplanted patients with chronic renal failure (Tx-CRF), 10 kidney-transplanted patients with normal renal function (Tx-N) and 10 controls (Ctr). The groups were comparable with respect to age and gender. The following glycoxydative stress markers were determined by HPLC analysis: albumin-bound and free pentosidine, low-molecular weight-advanced glycation end products (LMW-AGEs), advanced oxidation protein products (AOPP) and low-molecular weight carbonyls (LMW-C). The total antioxidant serum capacity was monitored by measuring both the ferric reducing/antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC). RESULTS: With respect to the controls, the Tx-CRF patients had higher levels of pentosidine (2.66 +/- 0.98 vs 1.45 +/- 1.1 pmol/mg), LMW-AGE (47.55 +/- 39.74 vs 15.45 +/- 6.39 a.u./ml), and AOPP (6.71 +/- 0.78 vs 4.81 +/- 0.32 a.u./mg) while Tx patients with normal kidney function had levels of these compounds that were comparable to the controls, except for the LMW-AGEs which were higher. Levels of LMW-AGEs, pentosidine, LMW-C and AOPP were inversely correlated to creatinine clearance. The total antioxidation serum capacity was paradoxically higher in Tx patients than in the controls, regardless of kidney function. FRAP as well as ORAC, were correlated to uric acid (r = 0.62, p < 0.001; r = 0.54, p < 0.01). CONCLUSIONS: The reported data indicate that kidney transplantation seems to restore a nearly normal level of glycoxidative stress markers, but a complete remission is only possible when the renal function is normal. An increase of total antioxidant power of serum in transplanted patients was reported, as probable effect of uric acid high levels.

Comparison between oscillometric and auscultatory methods of ambulatory blood pressure measurement in hemodialysis patients.

INTRODUCTION: 24-hour ambulatory blood pressure monitoring (ABPM) is commonly used in clinical and research practice. Different methods have been used in BP recording, cuff-oscillometric or Korotkoff sound, and validation studies during ABPM have been performed on general as well as hypertensive populations. Hemodialysis (HD) patients have a high percentage of complications, such as vascular diseases, and they are subject to hyperkinetic blood flows and abrupt body weight changes secondary to HD, which can invalidate BP recording. Therefore, we wanted to compare the 2 methods on an HD population. PATIENTS AND METHODS: We performed 86 ABPMs on 44 patients (aged 60.8 +/- 17.2 years) by using a device capable of the simultaneous recording of oscillometric and auscultatory BP (A&D Takeda TM2421). The data obtained with the 2 different ABPM methods have been compared, and the differences between auscultatory and oscillometric determinations have been analyzed, as presented by Bland and Altman [1986]. RESULTS: The percentage of valid recordings was significantly higher with the oscillometric method than with the auscultatory method (93.6 +/- 11.3% vs. 71.7 +/- 17.04%, p < 0.001). 24-hour diastolic BP and night-time systolic BP were higher when recorded with the oscillometric method (DBP = 75.4 +/- 9.6 mmHg vs. 71.8 +/- 9.6 mmHg, p < 0.001, asleep SBP = 119.7+/-23.3 mmHg vs. 116.2 +/- 25.0 mmHg, p < 0.001), and the systolic night/day BP ratio was also higher(0.92 +/- 0.10vs.0.90 +/- 0.10, p < 0.001). Finally, the BP coefficient of variation ((SD/mean BP) x 100) was higher when auscultatory determinations were used (16.1 +/- 4.6 vs. 14.6 +/- 4.9). The limits of agreement between auscultatory and oscillometric BP determinations were for SBP = -6.44; 7.84 and for DBP = -3.66; 10.86. CONCLUSIONS: Differences between 24-hour oscillometric and auscultatory ABPM were reported in HD patients: the diastolic 24-hour and asleep systolic BP values and the systolic night/day ratio obtained with the oscillometric method were significantly higher. The higher coefficient of variation reported with the auscultatory method and the wider limits of agreement suggest that the 2 methods do not fully coincide and, in our opinion, the oscillometric method is preferable, due to the higher number of 24-hour valid measurements.

Short daily hemodialysis: blood pressure control and left ventricular mass reduction in hypertensive hemodialysis patients.

Several retrospective and uncontrolled prospective studies reported blood pressure (BP) normalization and left ventricular mass (LVM) reduction during daily hemodialysis (DHD). Conversely, the burden of these major independent risk factors is only marginally reduced by the initiation of standard thrice-weekly dialysis (SHD), and cardiovascular events still represent the most common cause of death in hemodialysis patients. Therefore, we performed a randomized two-period crossover study to compare the effect of short DHD versus SHD on BP and LVM in hypertensive patients with end-stage renal disease. We studied 12 hypertensive patients who had been stable on SHD treatment for more than 6 months. At the end of 6 months of SHD and 6 months of DHD in a sequence of randomly assigned 24-hour ambulatory BP monitoring, echocardiography and bioimpedance were performed. Throughout the study, patients maintained the same Kt/V. A significant reduction in 24-hour BP during DHD was reported (systolic BP [SBP]: DHD, 128 +/- 11.6 mm Hg; SHD, 148 +/- 19.2 mm Hg; P < 0.01; diastolic BP: DHD, 67 +/- 8.3 mm Hg; SHD, 73 +/- 5.4 mm Hg; P = 0.01). The decrease in BP was accompanied by the withdrawal of antihypertensive therapy in 7 of 8 patients during DHD (P < 0.01). LVM index (LVMI) decreased significantly during DHD (DHD, 120.1 +/- 60.4 g/m(2); SHD, 148.7 +/- 59.7 g/m(2); P = 0.01). Extracellular water (ECW) content decreased from 52.7% +/- 11.4% to 47.6% +/- 7.5% (P = 0.02) and correlated with 24-hour SBP (r = 0.63; P < 0.01) and LVMI (r = 0.66; P < 0.01). In conclusion, this prospective crossover study confirms that DHD allows optimal control of BP, reduction in LVMI, and withdrawal of antihypertensive treatment. These effects seem to be related to reduction in ECW content.

Advanced glycation end products: specific fluorescence changes of pentosidine-like compounds during short daily hemodialysis.

BACKGROUND: Advanced glycation end products (AGE) accumulate in uremia and represent an important etiopathogenetic cause of morbidity in dialyzed patients. Conventional hemodialysis treatment seems to be ineffective in lowering AGE levels. We wished to investigate whether daily hemodialysis (DHD), a treatment that seems to result in better clinical condition in end-stage renal disease patients, is effective in the reduction of these compounds. METHODS: We evaluated 10 non-diabetic patients on standard hemodialysis (SHD = 3 x 4 h/week) for more than 6 months by a crossover study. These patients were assigned randomly to 6 months of DHD (6 x 2 h/week) or 6 months of SHD. Then, they were switched to 6 months of the alternative treatment. At the end of these two periods, we studied pentosidine-like AGE compounds by measuring the total fluorescence at a wavelength characteristic for these substances: Ex: 335nm/Em:385nm; we also measured protein-linked pentosidine at the same time points. Finally, we determined the AGE-related total fluorescence in the deproteinized serum of 13 uremic patients on peritoneal dialysis (CAPD) and of 10 healthy controls. RESULTS: Pre-HD AGE-related total fluorescence obtained after 6 months of DHD was significantly lower than that obtained with standard HD (DHD = 201.3 +/- 36.4 AU/ml vs. SHD = 267.5 +/- 141.4 AU/ml, p = 0.03). The extraction rate per minute of dialysis was slightly, but not significantly higher during DHD than SHD (0.29 +/- 0.11% vs. 0.23 +/- 0.04, p = 0.07). AGE-related total fluorescence pre-HD values in patients treated by SHD and DHD were about 20-fold higher than in control subjects. They did not differ from CAPD patients. The pre-dialysis level of protein-linked pentosidine was significantly lower in DHD than in SHD (DHD = 16.12 +/- 4.71 pmol/mg protein, SHD = 22.64 +/- 6.86 pmol/mg protein, p < 0.01). CONCLUSIONS: DHD showed a reduction in AGE-related total fluorescence, although the mean value remained higher than in control subjects. DHD is also accompanied by a decrease in protein-linked pentosidine.

Reduction of renal functional reserve in kidney transplant recipients: a possible role of arachidonic acid metabolism alterations.

AIM: Renal functional reserve (RFR), resulting from an increase in glomerular filtration (GFR) after protein load, is a matter of debate. In kidney transplant recipients most studies have failed to show conclusive results, reporting either the absence, the reduction or the presence of renal reserve in normo-functioning kidneys. The aim of this study was to investigate RFR in kidney transplant patients as well as the possible hormonal vasoactive alterations underlying the reduction of renal reserve reported in some patients. PATIENTS AND METHODS: We studied 8 controls and 25 patients, the latter with no history of acute rejection for at least 12 months and GFR >50 ml/min. The 25 patients were divided into 2 groups based on the presence (10) or the absence (15) of RFR. RESULTS: Both the RFR group and the controls experienced a similar increase of GFR after oral protein load: 24.3 +/- 15.57% vs 24.4 +/- 10.8%. The group without RFR showed a paradoxical reduction of GFR after oral protein load: 13.3 +/- 13.2% (p <0.001). We analyzed the filtration fraction (FF) and observed that the group without RFR had higher values than the group with RFR and the controls: 0.35 +/- 0.11 vs 0.29 +/- 0.07 (p = 0.01) and vs 0.26 +/- 0.02 (p = 0.04). The hyperfiltration state observed in the group without RFR was sustained by a high level of thromboxane. The urine ratio TxB2/6ketoPgF1alpha was higher in the group without RFR than in the RFR group 0.78 +/- 0.2 vs 0.64 +/- 0.1 (p = 0.01). This ratio decreased only in the RFR group after a meat meal. In all the patients, changes of TxB2/6ketoPGF1alpha were inversely correlated to changes of GFR after a meat meal (r = -0.6, p = 0.01). CONCLUSIONS: In conclusion, these data demonstrate that kidney transplant recipients with good organ function can be grouped according to the presence of RFR. RFR appears to be inversely correlated with the TxB2/6ketoPGF1alpha ratio, and its decrease seems to be linked to the failure of thromboxane to decrease and prostacycline to increase after a meat meal.

Comparison of target organ damage in renovascular and essential hypertension.

In many reports, the prevalence of target organ damage in renovascular hypertension (RVH) appears to be higher than in essential hypertension (EH). Since in most studies the renal artery stenosis is part of a diffuse atherosclerotic disease, it is not known whether these complications are due to RVH itself or to the vascular disease. We have undertaken a case control study of 92 patients divided into two groups (46 in each), one with RVH and the other with EH and abdominal aortic aneurysm, with a comparable degree of diffuse atherosclerotic vascular disease. The vascular state of the extracranial carotid arteries and abdominal and inferior limb districts was investigated with angiography and sonography. The prevalence of left ventricular hypertrophy (LVH) and ischemic heart disease (IHD) were assessed by electrocardiography. Serum creatinine and urinary protein excretion were employed in the renal evaluation. While the analysis of the results confirmed an even diffusion of atherosclerotic vascular disease between the two groups, a significant difference was found in the prevalence of heart and renal damage. LVH was present in 32.6% of RVH patients versus 10.8% in EH (P = .02). Serum creatinine > 1.4 mg/dL was found in 50% of RVH and in 23.9% of EH, (P = .01). The prevalence of proteinuria in RVH was also higher although not reaching the statistical significance. The results suggest that, in patients with comparable degrees of atherosclerotic vascular disease, RVH is responsible for the higher prevalence of target organ damage in this condition compared to those with EH.

Renal funtional reserve in kidney transplant recipients.

In the last few years different authors have observed that kidney transplant recipients with good organ function do not have a renal functional reserve (RFR). This condition is accompained by a high glomerular filtration rate (GFR). We studied RFR in patients with very good organ function under different immunosuppressive therapies, who were divided into groups based on the presence or absence of RFR.